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Biomedical subjects

Lisa Smith

Publications and source records attributed to Lisa Smith.

At least 19 recordsLinked to original sources
PubMed2006

A preliminary study of cortisol and norepinephrine reactivity to psychosocial stress in borderline personality disorder with high and low dissociation.

The goal of the current study was to investigate subjective and neurohormonal reactivity to acute psychosocial stress in borderline personality disorder (BPD) as a function of dissociative symptoms. Five BPD subjects with high dissociation, 8 BPD subjects with low dissociation, and 11 healthy control subjects were compared in basal urinary cortisol and norepinephrine, as well as in plasma cortisol and norepinephrine reactivity to the Trier Social Stress Test (TSST). Subjective stress rating and emotional response to the TSST were also measured. The three groups differed significantly in cortisol stress reactivity, with the high-dissociation BPD group demonstrating the most robust response. The three groups did not significantly differ in norepinephrine stress reactivity. In the combined BPD sample, dissociation severity tended to be inversely correlated with basal urinary norepinephrine, was positively correlated with norepinephrine stress reactivity. Childhood trauma was inversely correlated with basal urinary cortisol. In conclusion, despite its small sample size this pilot study suggests that dissociative symptomatology may be a marker of heightened biological vulnerability to stress in BPD, and merits further study.

Acute Disease↗
PubMed2006

Epidemiologic investigation of a cluster of workplace HIV infections in the adult film industry: Los Angeles, California, 2004.

BACKGROUND: Adult film production is a legal, multibillion dollar industry in California. In response to reports of human immunodeficiency virus (HIV) transmission by an adult film worker, we sought to determine the extent of HIV infection among exposed workers and to identify means of improving worker safety. METHODS: The Los Angeles County Department of Health Services initiated an outbreak investigation that included interviews of infected workers to elicit information about recent sex partners, review of the testing agency's medical records and laboratory results, molecular analysis of HIV isolates from the 4 infected workers, and a risk assessment of HIV transmission in the adult film industry. RESULTS: Many adult film workers participate in a monthly program of screening for HIV infection by means of polymerase chain reaction-based technology to detect HIV DNA in blood. A male performer tested negative for HIV on 12 February 2004 and 17 March 2004, then tested positive for HIV on 9 April 2004. During the period between the negative test results, he experienced a flulike illness after performing unprotected vaginal and anal intercourse for an adult film produced outside the United States by a US company. After returning to California, he performed unprotected sex acts for adult films with 13 female partners who had all tested negative for HIV in the preceding 30 days; 3 subsequently tested positive for HIV (a 23% attack rate). Contact tracing identified no reasonable sources of infection other than the male index patient. CONCLUSION: Although current testing methods may shorten the window period to diagnosis of new HIV infection, they fail to prevent occupational acquisition of HIV in this setting. A California Occupational Safety and Health Administration-approved written health and safety program that emphasizes primary prevention is needed for this industry.

Adult↗
PubMed2006

Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia.

Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (>70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

Adult↗
PubMed2006

Enhanced visual experiences and seeing hardware for reduced vision: a pilot study.

BACKGROUND: Persons with vision loss may have limited ability to experience visual arts and difficulty navigating unfamiliar environments. The Center for Advanced Visual Studies at Massachusetts Institute of Technology developed a Retinal Imaging Machine Vision System (RIMVS) "seeing machine" to project "word-images" onto the retina and permit navigation through virtual architectural environments. METHODS: Ten subjects with visual acuity < or = 20/70 in the better-seeing eye were recruited. Subjects viewed word-images that were projected on the retina of the better-seeing eye and asked to interpret the images. Subsequently, they were asked to recall as many images as possible. Participants also practiced navigation through a computer-modeled building that was projected onto the retina. A survey elicited subject response to the RIMVS. RESULTS: Six subjects correctly interpreted all 10 word-images; no subject interpreted fewer than 8 correctly. Seven subjects felt that the word images afforded easy recall, and 7 subjects responded that the technology might assist subsequent navigation in unfamiliar environments. CONCLUSIONS: Responses reflect a general interest and potential with the RIMVS. Further studies are warranted to explore the value of the RIMVS as a tool to enable visually compromised persons to experience and appreciate visual arts and as a navigation aid.

Adult↗
PubMed2006

The relative duties of a man: domestic medicine in England and France, ca. 1685-1740.

Although much work is currently being done on early modern women and household medicine and on early modern masculinities, historians have generally overlooked men's roles within the home, particularly with respect to domestic medical activities. Using medical consultation letters, this article examines men's roles as domestic caregivers and their medical decision making. During this period, manly self-management and household order were closely linked; an ideal head of household would manage himself retain order within the household, and look after the welfare of his family.

Caregivers↗
PubMed2005

Glutamate modulators as novel interventions for mood disorders.

UNLABELLED: Recent evidence suggests that critical molecules in neurotrophic signaling cascades are long-term targets for currently available monoaminergic antidepressants. As chronic and severe mood disorders are characterized by impairments in neuronal resilience, pharmacological strategies that subserve a neuroprotective function might alter disorder pathophysiology and modify disease progression. Several promising approaches involve modulation of the glutamate neurotransmitter system, via post-synaptic receptor blockade or potentiation and presynaptic vesicular release inhibition. A focused review of the extant scientific literature was conducted, with a discussion of 3 compounds or classes of drugs currently undergoing clinical investigation: ketamine, riluzole, and AMPA receptor potentiators. Recent investigations in mood disordered patients suggest that the NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Riluzole has been shown to reverse glutamate-mediated impairments in neuronal plasticity and to stimulate the synthesis of brain derived neurotrophic factor. Open-label trials in treatment-resistant depression have yielded promising results. Likewise, AMPA receptor potentiators favorably impact neurotrophic factors as well as enhance cognition. CONCLUSIONS: Pharmacological approaches that modulate components of the glutamate system offer novel targets for severe, recurrent mood disorders. Controlled studies are necessary.

Animals↗
PubMed2004

Epigenetic profiling in chronic lymphocytic leukemia reveals novel methylation targets.

CpG island methylation is an epigenetic alteration that contributes to tumorigenesis by transcriptional inactivation of genes. Little is known about the overall levels of CpG island methylation in chronic lymphocytic leukemia (CLL). To provide a baseline estimate of global aberrant methylation and identify target sequences for additional investigation, we performed Restriction Landmark Genomic Scanning on 10 CLL samples. Two methylation-sensitive landmark enzymes were used (NotI and AscI), allowing assessment of over 3000 CpG islands in each sample. Tumor-derived Restriction Landmark Genomic Scanning profiles were compared with profiles from CD19-selected B cells from normal volunteers and matched normal neutrophils from 4 CLL patients. We found 2.5-8.1% (mean 4.8%) of the CpG islands in CLL samples were aberrantly methylated compared with controls, and the methylation events had a nonrandom distribution (P < 0.0001). Furthermore, we identified 193 aberrantly methylated sequences, of which 93% have CpG island characteristics and 90% have homology to genes or expressed sequences. One such gene, the G protein-coupled metabotropic glutamate receptor 7 (GRM7), possibly inhibits cyclic AMP signaling in the induction of apoptosis. Bisulfite sequencing of GRM7 confirmed extensive CpG island methylation, and treatment with 5-aza-2'-deoxycytidine (decitabine) resulted in up-regulated expression of several genes in vitro with concurrent cellular depletion of DNMT1 protein. Our dual-enzyme global methylation study shows that CLL is characterized by widespread nonrandom CpG island methylation similar to other tumors and provides a panel of novel methylation targets that can be used in larger studies designed to assess impact on disease progression and survival.

Adult↗
PubMed2004

Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions.

The presence of p53 mutation or deletion predicts for poor response to conventional therapy in chronic lymphocytic leukemia (CLL). We sought to determine whether the humanized anti-CD52 antibody alemtuzumab was effective in this patient group. Thirty-six patients with fludarabine-refractory CLL were treated with alemtuzumab, 15 (42%) of whom had p53 mutations or deletions. Clinical responses in patients with p53 mutations, deletions, or both were noted in 6 (40%) of 15 versus 4 (19%) of 21 of patients without. The median response duration for this subset of patients was 8 months (range, 3-17 months). These data suggest that alemtuzumab may be an effective therapy for patients with CLL with p53 mutations or deletions.

Aged↗
PubMed2004

Nitrous oxide analgesia for minor pediatric surgical procedures: an effective alternative to conscious sedation?

BACKGROUND/PURPOSE: Minor surgical procedures in children, while usually not requiring general anesthesia, need effective control of pain, anxiety, and motion. Certain techniques of conscious sedation may result in loss of protective airway reflexes. Nitrous oxide, however, when inhaled at levels below 50% maintains protective reflexes and does not require fasting or postprocedure monitoring. This study prospectively examines the efficacy of nitrous oxide analgesia in children undergoing outpatient surgical procedures. METHODS: Over a 2-year period (2000 to 2002), 150 consecutive children were given nitrous oxide analgesia as an alternative to a general anesthetic, sedation, or local anesthetic alone. Nitrous oxide (<50%) was administered by our practice's sedation-certified nurse practitioner without an anesthesiologist present. The children used the Wong-Baker Faces Scale (0-5) to score pain at different intervals (preprocedure, at injection, during procedure, and postprocedure) and event memories were tabulated. RESULTS: Of 150 children, 5 were uncooperative and could not participate. One hundred forty-five children, ages 1 to 20 years (Mean, 9.83 +/- 4.92 years) successfully underwent procedures (58 cyst/nevus excisions, 49 abscess drainages, 38 other) using nitrous. Two patients were too young to score pain. Pre- and postprocedure pain scores were significantly higher in the abscess group (P <.0001); during the procedures, however, all groups reported pain scores less than 1, with parents citing 100% satisfaction with the technique. Of 128 children receiving local anesthesia, 107 (84%) had no recall of the injection. Complications were limited to 4 patients; 2 experienced nausea, and 2 vomited. All resolved without interrupting the procedure. CONCLUSIONS: Nitrous oxide analgesia is a cost-effective and efficacious alternative to conscious sedation or general anesthesia for minor pediatric surgical procedures. In the office or outpatient setting, the technique provides for almost pain/anxiety-free surgery, no postoperative monitoring, and a high degree of satisfaction for patients, parents, and staff.

Adolescent↗
PubMed2004

Correlates of Internet use to meet sex partners among men who have sex with men diagnosed with early syphilis in Los Angeles County.

OBJECTIVE: The objective of this study was to evaluate use of the Internet to solicit sex partners by men who have sex with men (MSM) who were diagnosed with early syphilis infection. STUDY: Field interview records for syphilis patients were reviewed for factors associated with Internet use. RESULTS: Internet users were more likely to be of white race (prevalence ratio [PR], 1.6; 95% confidence interval [CI], 1.4-1.8), to report anal insertive sex (PR, 1.1; 95% CI, 1.1-1.2), sex with anonymous partners (PR, 1.2; 95% CI, 1.1-1.3), intravenous drug use (PR, 2.7; 95% CI, 1.1-6.7), and nonintravenous drug use (PR, 1.4; 95% CI, 1.1-1.8). Controlling for race and sexual risk behaviors, white race (odds ratio [OR], 2.8; 95% CI, 1.8-4.6), having anonymous sex partners (OR, 3.4; 95% CI, 1.6-7.0), and nonintravenous drug use (OR, 1.6; 95% CI, 1.1-2.6) were associated with meeting sex partners through the Internet. CONCLUSIONS: Effective sexually transmitted disease risk reduction interventions using the Internet are needed to reach Internet-using, sex-seeking MSM populations engaging in high-risk behaviors.

Adult↗
PubMed2004

Cysticercosis-related deaths, California.

Cysticercosis is an increasingly important disease in the United States, but information on the occurrence of related deaths is limited. We examined data from California death certificates for the 12-year period 1989-2000. A total of 124 cysticercosis deaths were identified, representing a crude 12-year death rate of 3.9 per million population (95% confidence interval [CI] 3.2 to 4.6). Eighty-two (66%) of the case-patients were male; 42 (34%) were female. The median age at death was 34.5 years (range 7-81 years). Most patients (107, 86.3%) were foreign-born, and 90 (72.6%) had emigrated from Mexico. Seventeen (13.7%) deaths occurred in U.S.-born residents. Cysticercosis death rates were higher in Latino residents of California (13.0/106) than in other racial/ethnic groups (0.4/106), in males (5.2/106) than in females (2.7/106), and in persons >14 years of age (5.0/106). Cysticercosis is a preventable cause of premature death, particularly among young Latino persons in California and may be a more common cause of death in the United States than previously recognized.

Adolescent↗
PubMed2003

Interphase cytogenetic abnormalities in chronic lymphocytic leukemia may predict response to rituximab.

Select cytogenetic abnormalities such as del(17)(p13.1) and del(11)(q22-q23)predict rapid disease progression and inferior survival in chronic lymphocytic leukemia (CLL). We sought to determine the impact of the four most common interphase cytogenetic abnormalities in 28 CLL patients relative to response to three-times-a-week rituximab therapy. Abnormalities were noted in 25 of the 28 patients to include del(13)(q14.3) [n = 16 (57%)], del(11)(q22.3) [n = 10 (36%)], +12 [n = 6 (21%)], del(17)(p13.1) [n = 5 (18%)], and normal [n = 3 (11%)]. Only a minority of each of these occurred as sole abnormalities. To categorize patients into one specific group, we used the hierarchical order del(17)(p13.1) > del(11)(q22.3) > trisomy 12 > del(13)(q14.3) to prioritize. Response to rituximab was noted to vary by cytogenetic group: del(17)(p13.1), 0% [n = 5]; del(11)(q22.3), 66% [n = 9]; del(13)(q14.3), 86% [n = 7]; +12, 25% [n = 4], and normal, 0% [n = 3]. Response was significantly lower (P = 0.05) in patients with del(17)(p13.1) as compared with those with other abnormalities. These data suggest that interphase cytogenetics in CLL may be predictive of a response to rituximab therapy and provide support for additional studies validating risk-adapted therapy in this disease.

Antibodies, Monoclonal↗
PubMed2003

Ocular allergic disease: mechanisms, disease sub-types, treatment.

Ocular allergy refers to a variety of hypersensitivity disorders that affect the lid, conjunctiva, and/or cornea. Its incidence is estimated at over 20% of the general population in the United States. This review will discuss the various forms of ocular allergy, their pathophysiology, clinical presentation, and treatment. New frontiers in mechanisms, therapy, and management in the office are emphasized throughout.

Journal Article↗
PubMed2002

The incidence and influence of early traumatic life events in patients with panic disorder: a comparison with other psychiatric outpatients.

Early traumatic life events, including childhood physical and sexual abuse, has been associated with increased risk for panic disorder in adulthood. We examined the incidence and influence of early traumatic life events in outpatients with panic disorder (n = 101), compared to outpatients with other anxiety disorders (n = 58), major depression (n = 19), or chronic schizophrenia (n = 22). Data were obtained by means of Structured Clinical Interviews and self-report questionnaires. The incidence of childhood physical abuse ranged from 16 to 40% and for childhood sexual abuse from 13 to 43% with no significant differences among the four diagnostic groups. Across all outpatient groups a history of childhood physical or sexual abuse was positively correlated to clinical severity. Patients with panic disorder who reported childhood physical abuse were more likely to be diagnosed with comorbid depression, to have more comorbid Axis I disorders, to score higher on symptom checklists as well as reporting a greater history of suicide attempts in the past year (5% vs. 0%); or lifetime (36% vs. 15%). Similar findings were noted, but not as robustly, for patients with panic disorder who reported childhood sexual abuse. There is a high rate of adverse early childhood events across diagnostic groups in psychiatric outpatients and these events are likely to influence the severity of the disorder but are unlikely to be a unique risk factor for any one type of disorder.

Adult↗
PubMed2002

A novel beta-lactam antibiotic activates tumor cell apoptotic program by inducing DNA damage.

Many of the anticancer drugs in current use are toxic and thus limited in their efficacy. It therefore becomes essential to develop novel chemotherapeutic agents with lower levels of toxicity. The beta-lactam antibiotics have been used for many years to treat bacterial infections with limited or no toxicity. Until now, it has never been shown that beta-lactams could kill tumor cells. Here, for the first time, we have discovered and characterized the apoptosis-inducing properties of a family of novel beta-lactam antibiotics against human leukemia, breast, prostate, and head-and-neck cancer cells. We found that one particular lead compound (lactam 1) with an N-methylthio group was able to induce DNA damage and inhibit DNA replication in Jurkat T cells within a 2-h treatment. This was followed by p38 mitogen-activated protein kinase activation, S phase arrest, and apoptotic cell death. p38 was found to be a central player in beta-lactam-induced apoptosis and resided downstream of DNA damage but upstream of caspase activation. Accompanying caspase-8 activation was cleavage of the pro-apoptotic Bcl-2 family protein Bid, and release of the mitochondrial cytochrome c. This was also associated with activation of caspase-9 and -3. Analogs of lactam 1 in which the N-methylthio group was replaced with other organothio chains exhibited progressive decreased potencies to induce DNA damage, p38 kinase activation, S phase arrest, and apoptosis, demonstrating requirement of the N-methylthio group. Because of the ease of synthesis and structural manipulation, we believe these beta-lactams may have the potential to be developed into anticancer agents.

Anti-Bacterial Agents↗
PubMedDate not supplied

Clinical practice guideline adherence before and after implementation of the HEARTFELT (HEART Failure Effectiveness & Leadership Team) intervention.

HEART Failure Effectiveness & Leadership Team (HEARTFELT) is a multifaceted intervention designed to improve adherence with the American College of Cardiology/American Heart Association practice guidelines for heart failure (HF). The purpose of this study was to assess differences in clinician adherence with clinical practice guidelines before and after implementation of HEARTFELT. A quasi-experimental, untreated control group design with separate pretest/posttest samples was employed at a community hospital in Connecticut. The untreated historical control group included patients aged 65 years or older with HF and a nonequivalent comparison group of patients with stroke. The posttest samples included patients with the diagnosis of HF and stroke admitted after implementation of the HEARTFELT intervention. The HEARTFELT intervention included automated pathway in electronic medical record (order sets, interdisciplinary plan of care, self-management plan), access to evidence for clinicians and patients, HF self-management education tools, and ongoing discipline-specific feedback regarding adherence. Data were analyzed using parametric and nonparametric methods. The HEARTFELT intervention significantly improved clinician adherence with addressing all self-management categories in the electronic medical record (P = .000) and adherence with self-management education given to the patient in writing at discharge (P = .000). There were no significant differences in adherence with medical interventions (P = .39). While guideline adherence is associated with less practice variation and improved processes, methods of integration into practice in community hospital settings have been largely unexplored. The multifaceted HEARTFELT intervention is promising for its potential to integrate evidence at the point of care, to reduce unwarranted variation in practice, and ultimately to improve the outcomes of individuals with HF.

Aged↗
PubMedDate not supplied

Implementing personal digital assistant documentation of pharmacist interventions in a military treatment facility.

OBJECTIVE: To describe the use of personal digital assistants (PDAs) in documenting pharmacists' clinical interventions. SETTING: Evans Army Community Hospital (EACH), a 78-bed military treatment facility, in Colorado Springs. PARTICIPANTS: Pharmacists on staff at EACH. PRACTICE DESCRIPTION: All pharmacists at EACH used PDAs with the pilot software to record interventions for 1 month. The program underwent final design changes and then became the sole source for recording pharmacist interventions. The results of this project are being evaluated every 3 months for the first year and yearly thereafter. PRACTICE INNOVATION: Visual CE (Syware Inc. Cambridge, Mass.) software was selected to develop fields for the documentation tool. This software is simple and easy to use, and users can retrieve reports of interventions from both inpatient and outpatient sections. The software needed to be designed so that data entry would only take a few minutes and ad hoc reports could be produced easily. MAIN OUTCOME MEASURES: Number of pharmacist interventions reported, time spent in clinical interventions, and outcome of clinical intervention. RESULTS: Implementing a PDA-based system for documenting pharmacist interventions across ambulatory, inpatient, and clinical services dramatically increased reporting during the first 6 months after implementation (August 2004-February 2005). After initial fielding, clinical pharmacists in advanced practice settings (such as disease management clinic, anticoagulation clinic) recognized a need to tailor the program to their specific activities, which resulted in a spin-off program unique to their practice roles. CONCLUSION: A PDA-based system for documenting clinical interventions at a military treatment facility increased reporting of interventions across all pharmacy points of service. Pharmacy leadership used these data to document the impact of pharmacist interventions on safety and quality of pharmaceutical care provided.

Computers, Handheld↗